Effect of gallium nitrate on the expression of osteoprotegerin and receptor activator of nuclear factor-kappa B ligand in osteoblasts in vivo and in vitro

摘要

Osteoporosis is characterized by the progressive loss of bone mass and the micro-architectural deterioration of bone tissue, leading to bone fragility and an increased risk of fracture. Gallium has demonstrated efficacy in the treatment of several diverse disorders that are characterized by accelerated bone loss. Osteoblasts orchestrate bone degradation by expressing the receptor activator of NF-kappa B ligand (RANKL), however they additionally protect the skeleton by secreting osteoprotegerin (OPG). Therefore, the relative concentration of RANKL and OPG in bone is a key determinant of bone mass and strength. The current study demonstrated that gallium nitrate (GaN) is able to counteract bone loss in an experimental model of established osteoporosis. Ovariectomized (OVX) rats exhibited significantly increased bone mineral density following GaN treatment for 4 and 8 weeks by 19.3 and 37.3%, respectively (P<0.05). The bone volume of the OVX + GaN group was increased by 40.9% (P<0.05) compared with the OVX group. In addition, the current study demonstrated that GaN stimulates the synthesis of OPG however has no effect on the expression of RANKL in osteoblasts, as demonstrated by RT-qPCR, western blotting and ELISA, resulting in an increase in the OPG/RANKL ratio and a reduction in osteoclast differentiation in vivo and in vitro.